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BMC Developmental Biology

, 7:124

First Online: 07 November 2007Received: 15 June 2007Accepted: 07 November 2007


BackgroundIt has been well established that human fetuses will heal cutaneous wounds with perfect regeneration. Insulin-like growth factors are pro-fibrotic fibroblast mitogens that have important roles in both adult wound healing and during development, although their relative contribution towards fetal wound healing is currently unknown. We have compared responses to IGF-I and -II in human dermal fibroblast strains derived from early gestational age fetal <14 weeks and developmentally mature postnatal skin to identify any differences that might relate to their respective wound healing responses of regeneration or fibrosis.

ResultsWe have established that the mitogenic response of fetal cells to both IGF-I and -II is much lower than that seen in postnatal dermal fibroblasts. Further, unlike postnatal cells, fetal cells fail to synthesise collagen in response to IGF-I, whereas they do increase synthesis in response to IGF-II. This apparent developmentally regulated difference in response to these related growth factors is also reflected in changes in the tyrosine phosphorylation pattern of a number of proteins. Postnatal cells exhibit a significant increase in phosphorylation of ERK 1 p44 in response to IGF-I and conversely the p46 isoform of Shc on IGF-II stimulation. Fetal cells however only show a significant increase in an unidentified 100 kDa tyrosine-phosphorylated protein on stimulation with IGF-II.

ConclusionDermal fibroblasts exhibit different responses to the two forms of IGF depending on their developmental maturity. This may relate to the developmental transition in cutaneous wound healing from regeneration to fibrosis.

AbbreviationsECMExtra cellular matrix

ERKExtra cellular signal regulated kinase

FCSFetal calf serum

FDFFetal dermal fibroblasts

IGF-IInsulin like growth factor -I

IGFIRInsulin like growth factor-I receptor

IGF-IIInsulin like growth factor II

MAPKMitogen activated protein kinase

NGMNormal growth media

MDFPostnatal dermal fibroblasts

SFMSerum free media

Electronic supplementary materialThe online version of this article doi:10.1186-1471-213X-7-124 contains supplementary material, which is available to authorized users.

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Autor: Kerstin J Rolfe - Alison D Cambrey - Janette Richardson - Laurie M Irvine - Adriaan O Grobbelaar - Claire Linge


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